Edinburgh Trials Methodology Hub

Lead Research Organisation: University of Edinburgh
Department Name: School of Clinical Sciences

Abstract

When a new drug is being developed it passes through several stages of development. After the initial preclinical development, first in man studies evaluate the safety and potential side effects. Then explanatory studies optimise the treatment, for example in terms of which patients have the greatest potential to benefit and what dose to use. Such studies look at underlying disease mechanisms, and test whether an intervention has the potential to be useful in practice. Then pragmatic studies test whether any potential benefit seen in the explanatory trials can be realised in clinical practice. For non-drug treatments the terminology is different, but the development path is similar.

There are many reasons why an intervention can fail as it progresses through the stages of development, and the aim of the Edinburgh Trials Methodology Hub is to undertake a programme of research which will help to increase the chances of success at each step of the development process. We shall attempt to learn lessons both from successful development programmes and also from others which have failed.

This will be achieved by encouraging interdisciplinary cllaboration between the scientists who are working on understanding underlying disease mechanisms and those with experience in clinical trials methodology. The end results will be to improve the design and analysis of future clinical trials, and to provide researchers with trials support and access to genetic and imaging technologies to identify patient subgroups with the greatest potential to benefit within ongoing trials.

Technical Summary

Our vision is to deliver more effective translation of novel scientific ideas and discoveries (both drug and non-drug) into innovative clinical practice. A major challenge in clinical medicine is to identify therapeutic interventions that can be targeted to the correct patient at the right time to substantially improve disease outcomes. Traditionally, clinical trial design has focussed on delivering a standardised intervention on a large scale to patients with a specific clinical presentation which may actually have several different underlying causes, in terms of pathophysiology. This approach has been successful to an extent, but often these interventions have modest effects for the individual patient. Ideally therefore, one would wish to develop biomarkers which can be used in clinical practice to predict which patients will have the greatest response to an intervention, whilst excluding those who are likely to respond poorly or not at all. The vision of the Edinburgh Clinical Trials Methodology Hub will be to develop technologies to achieve this aim, by exploiting knowledge gained from animal models; by developing grid based networks for image analysis and processing; by exploiting access to genomic technologies and by developing a facility for secondary analysis of existing data to develop and validate prognostic models. The end result will be to improve the design of future clinical trials and to provide researchers access to imaging and genetic technologies to identify patient subgroups who respond best within ongoing trials.

In parallel with the planned methodological developments, the Edinburgh Hub will develop a training programme which combines elements of existing programmes in translational medicine, molecular medicine and public health sciences to develop the next generation of trialists and methodologists.

Publications

10 25 50

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Andrews PJ (2015) Hypothermia for Intracranial Hypertension after Traumatic Brain Injury. in The New England journal of medicine

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Baskerville TA (2012) Noninvasive MRI measurement of CBF: evaluating an arterial spin labelling sequence with 99mTc-HMPAO CBF autoradiography in a rat stroke model. in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

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Bates TC (2009) Association of KIBRA and memory. in Neuroscience letters

 
Description Arthritis Research UK
Amount £756,791 (GBP)
Organisation Versus Arthritis 
Start 06/2010 
End 06/2013
 
Description Arthritis Research UK
Amount £723,692 (GBP)
Funding ID 19403 
Organisation Versus Arthritis 
Start 06/2010 
End 02/2016
 
Description CSO funding Health Services Research
Amount £224,999 (GBP)
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 01/2011 
End 03/2013
 
Description CSO funding Health Sevices Research
Amount £400,000 (GBP)
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 04/2010 
End 04/2012
 
Description Chief Scientist Office (CSO)
Amount £47,030 (GBP)
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start  
 
Description EME Programme
Amount £3,070,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2012 
End 06/2014
 
Description HTA Programme
Amount £2,140,000 (GBP)
Funding ID 11/01/1930 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2012 
End 05/2017
 
Description MRC Clinician Scientist Fellowship
Amount £834,329 (GBP)
Funding ID G0902303/95197 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2015
 
Description MRC Efficacy and Mechanism Evaluation Programme (EME)
Amount £1,000,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2010 
End 06/2014
 
Description MRC Methodology Research Panel
Amount £120,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2010 
End 06/2012
 
Description MRC NIHR
Amount £1,369,437 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2011 
End 04/2016
 
Description Medical Research Council Clinician Scientist Fellowship
Amount £834,329 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2015
 
Description NIHR HTA
Amount £2,940,842 (GBP)
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start  
 
Description NIHR HTA
Amount £485,908 (GBP)
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 07/2011 
End 08/2013
 
Description Project Grant
Amount £1,340,000 (GBP)
Funding ID SP/12/2/29422 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2013 
End 05/2018
 
Title Ordinal Analysis of Clinical Trial Outcomes 
Description A number of methodological studies, now supported by relevant publications, have demonstrated the strengths and limitations of ordinal analysis in clinical trials of head injury and stroke. 
Type Of Material Data analysis technique 
Year Produced 2009 
Provided To Others? Yes  
Impact An ordinal approach has been adopted as the primary analytical approach in a number of on-going clinical trials. 
 
Description Edinburgh Clinical Trials Unit 
Organisation University of Edinburgh
Department Edinburgh Clinical Trials Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution The senior statisticians with the Hub work closely with the Trials Unit, giving statistical input for trial protocols and grant applications.
Collaborator Contribution The collaboration has been a source of research questions for the Merthodology Hub and given the opportunity to evaluate and promote methodological developments emerging from the Methodology Hub.
Impact The principal outputs to date have been grant applications for clinical trials which have been funded - including awards through MRC EME, Arthritis Research UK, and CSO.
Start Year 2009
 
Description Scottish Mental Health Research Network 
Organisation Scottish Mental Health Research Network (SMHRN)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Hub statisticians are involved in giving statistical advice to researchers via the SMHRN's Protocol Development Groups.
Collaborator Contribution The protocols developed via the SMHRN provide a source of methodological research problemsand also a testbed for methodological innovations.
Impact The outputs to date have been grant applications being worked up for submission.
Start Year 2009
 
Description Scottish eHealth Informatics Research Centre 
Organisation Scottish School of Primary Care
Department Scottish eHealth Informatics Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution This is at a very early stage, with the eHIRC just having been funded.
Collaborator Contribution Sheikh is a grant holder for the eHIRC. The grant application to extend the Hub funding beyond 2013 has eHealth as a major research theme.
Impact It is too early for this collaboration to have produced outputs
Start Year 2012